Slowly lethal experimental cryptococcosis of guinea pigs caused specific lymphocyte unresponsiveness to cryptococcal antigen, similar to the cellular events of cryptococcosis in man. Severe cryptococcosis of man caused marked depletion of alternate pathway components, probably as a result of intense antigenemia. The collaborative group has admitted 34 patients into a study comparing combined 5-fluorocytosine - amphotericin B with amphotericin B therapy alone. Preliminary evidence indicated that both the therapeutic and toxic effects of 5-fluorocytosine may be due to inhibition of thymidylate synthetase.